Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
권호 표지
DOI QR코드

DOI QR Code

Collagen Type VII (COL7A1) as a Longevity Mediator in Caenorhabditis elegans: Anti-Aging Effects on Healthspan Extension and Skin Collagen Synthesis

  • Received : 2024.08.01
  • Accepted : 2024.09.30
  • Published : 2024.11.01
Download PDF
⟨ Previous Next ⟩

Abstract

Longevity genes and senescence-related signaling proteins are crucial targets in aging research, which aims to enhance the healthy period and quality of life. Identifying these target proteins remains challenging because of the need for precise categorization and validation methods. Our multifaceted approach combined bioinformatics with transcriptomic data to identify collagen as a key element associated with the lifespan of the model organism, Caenorhabditis elegans. By analyzing transcriptomic data from long-lived mutants that involved mechanisms such as antioxidation, dietary restriction, and genetic background, we identified collagen as a common longevity-associated gene. We validated these findings by confirming that collagen peptides positively affect lifespan, thereby strengthening the validity of the target. Further verification through healthspan factors in C. elegans and functional assays in skin fibroblasts provided additional evidence of the role of collagen in organismal aging. Specifically, our study revealed that collagen type VII is a significant target protein for mitigating age-related decline. By validating these findings across different aging models and cell-based studies, we present compelling evidence for the anti-aging effects of collagen type VII, highlighting its potential as a target for promoting healthy aging. This study proposes that collagen not only serves as an indicative marker of organismal longevity across various senescence-related signaling pathways, but also offers a mechanistic understanding of skin degeneration. Consequently, collagen is an effective target for interventions aimed at mitigating skin aging. This study underscores the potential of collagen type VII (bonding collagen T7) as a therapeutic target for enhancing skin health and overall longevity.

Keywords

Acknowledgement

This study was supported by Konkuk University in 2024. The analysis of COL7A1 protein was supported by the Gyeonggido Business & Science Accelerator (GBSA).

References

  1. Bolger, A. M., Lohse, M. and Usadel, B. (2014) Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114-2120.
  2. Calabrese, E. J., Nascarella, M., Pressman, P., Hayes, A. W., Dhawan, G., Kapoor, R., Calabrese, V. and Agathokleous, E. (2024) Hormesis determines lifespan. Ageing Res. Rev. 94, 102181.
  3. Cao, Q., Tartaglia, G., Alexander, M., Park, P. H., Poojan, S., Farshchian, M., Fuentes, I., Chen, M., McGrath, J. A., Palisson, F., SalasAlanis, J. and South, A. P. (2022) Collagen VII maintains proteostasis in dermal fibroblasts by scaffolding TANGO1 cargo. Matrix Biol. 111, 226-244.
  4. Chung, C. L., Lawrence, I., Hoffman, M., Elgindi, D., Nadhan, K., Potnis, M., Jin, A., Sershon, C., Binnebose, R., Lorenzini, A. and Sell, C. (2019) Topical rapamycin reduces markers of senescence and aging in human skin: an exploratory, prospective, randomized trial. Geroscience 41, 861-869.
  5. Chung, H. J. and Uitto, J. (2010) Type VII collagen: the anchoring fibril protein at fault in dystrophic epidermolysis bullosa. Dermatol. Clin. 28, 93-105.
  6. Gildner, C. D., Roy, D. C., Farrar, C. S. and Hocking, D. C. (2014) Opposing effects of collagen I and vitronectin on fibronectin fibril structure and function. Matrix Biol. 34, 33-45.
  7. Goldberg, M., Kulkarni, A. B., Young, M. and Boskey, A. (2011) Dentin: structure, composition and mineralization. Front. Biosci. (Elite Ed.) 3, 711-735.
  8. Gretzmeier, C., Pin, D., Kern, J. S., Chen, M., Woodley, D. T., Bruckner-Tuderman, L., de Souza, M. P. and Nystrom, A. (2022) Systemic collagen VII replacement therapy for advanced recessive dystrophic epidermolysis bullosa. J. Invest. Dermatol. 142, 1094-1102.e3.
  9. Lucanic, M., Plummer, W. T., Chen, E., Harke, J., Foulger, A. C., Onken, B., Coleman-Hulbert, A. L., Dumas, K. J., Guo, S., Johnson, E., Bhaumik, D., Xue, J., Crist, A. B., Presley, M. P., Harinath, G., Sedore, C. A., Chamoli, M., Kamat, S., Chen, M. K., Angeli, S., Chang, C., Willis, J. H., Edgar, D., Royal, M. A., Chao, E. A., Patel, S., Garrett, T., Ibanez-Ventoso, C., Hope, J., Kish, J. L., Guo, M., Lithgow, G. J., Driscoll, M. and Phillips, P. C. (2017) Impact of genetic background and experimental reproducibility on identifying chemical compounds with robust longevity effects. Nat. Commun. 8, 14256.
  10. Lwin, S. M. and McGrath, J. A. (2022) Restoring type VII collagen in skin. Med 3, 273-275.
  11. Oudart, J. B., Monboisse, J. C., Maquart, F. X., Brassart, B., Brassart-Pasco, S. and Ramont, L. (2017) Type XIX collagen: a new partner in the interactions between tumor cells and their microenvironment. Matrix Biol. 57-58, 169-177.
  12. Pertea, M., Kim, D., Pertea, G. M., Leek, J. T. and Salzberg, S. L. (2016) Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown. Nat. Protoc. 11, 1650-1667.
  13. Pertea, M., Pertea, G. M., Antonescu, C. M., Chang, T. C., Mendell, J. T. and Salzberg, S. L. (2015) StringTie enables improved reconstruction of a transcriptome from RNA-seq reads. Nat. Biotechnol. 33, 290-295.
  14. Rahimi, M., Sohrabi, S. and Murphy, C. T. (2022) Novel elasticity measurements reveal C. elegans cuticle stiffens with age and in a longlived mutant. Biophys. J. 121, 515-524.
  15. Rahmati, M., Nalesso, G., Mobasheri, A. and Mozafari, M. (2017) Aging and osteoarthritis: central role of the extracellular matrix. Ageing Res. Rev. 40, 20-30.
  16. Senchuk, M. M., Dues, D. J., Schaar, C. E., Johnson, B. K., Madaj, Z. B., Bowman, M. J., Winn, M. E. and Van Raamsdonk, J. M. (2018) Activation of DAF-16/FOXO by reactive oxygen species contributes to longevity in long-lived mitochondrial mutants in Caenorhabditis elegans. PLoS Genet. 14, e1007268.
  17. Sorushanova, A., Delgado, L. M., Wu, Z., Shologu, N., Kshirsagar, A., Raghunath, R., Mullen, A. M., Bayon, Y., Pandit, A., Raghunath, M. and Zeugolis, D. I. (2019) The collagen suprafamily: from biosynthesis to advanced biomaterial development. Adv. Mater. 31, e1801651.
  18. Stein, K. C., Morales-Polanco, F., van der Lienden, J., Rainbolt, T. K. and Frydman, J. (2022) Ageing exacerbates ribosome pausing to disrupt cotranslational proteostasis. Nature 601, 637-642.
  19. Teuscher, A. C., Statzer, C., Goyala, A., Domenig, S. A., Schoen, I., Hess, M., Hofer, A. M., Fossati, A., Vogel, V., Goksel, O., Aebersold, R. and Ewald, C. Y. (2024) Longevity interventions modulate mechanotransduction and extracellular matrix homeostasis in C. elegans. Nat. Commun. 15, 276.
  20. Tohgasaki, T., Nishizawa, S., Kondo, S., Ishiwatari, S. and Sakurai, T. (2022) Long hanging structure of collagen VII connects the elastic fibers and the basement membrane in young skin tissue. J. Histochem. Cytochem. 70, 751-757.
  21. Tuckwell, D. (2002) Identification and analysis of collagen alpha 1(XXI), a novel member of the FACIT collagen family. Matrix Biol. 21, 63-66.